Avian and mammalian reoviruses comprise the genus Orthoreovirus in the family Reoviridae. These viruses contain 10 dsRNA genome segments enclosed within a non-enveloped, icosahedral double capsid of approximately 80 nm (Joklik, W. K. In: The reoviridae. W. K. Joklik, ed. Plenum Press, New York, pp. 9-78, 1983; Schnitzer, T. J. et al. J. Virol. 43: 1006-1014, 1982). The genome segments can be separated based on electrophoretic mobility into three large (L1,2,3), three medium (M1,2,3) and four small (S1,2,3,4) segments which encode proteins λ1, λ2, λ3, μ1, μ2, μNS, σ3, σ1, σ2, σNS, respectively (Spandidos D. A., and Graham, A. F., J. Virol. 19: 968-976, 1976; Varela, R. and Benavente, J., J. Virol. 68: 6775-6777, 1994; Wu, W. Y. et al., J. Virol. Methods 48: 119-122, 1994). The σ2 protein is an outer capsid protein which carries group-specific neutralizing epitopes, binds double-stranded RNA, and has been identified as a zinc metalloprotein (Wickramsinghe et al., Virology 194:688-696, 1993; Nibert, M. L. and Schiff, L. A., In: Fields virology, 4th ed., vol. 2. Knipe, D. M., and Howley, P. M., eds. Lippincott Williams & Wilkins, Philadelphia, Pa., p. 3087, 2001).
Avian reoviruses (ARV) are a diverse group of poultry pathogens whose virulence varies greatly, among isolates within different hosts. ARVs have been isolated from turkeys with poult enteritis and mortality syndrome (PEMS) (Heggen-Peay, C. L., et al., Avian Dis. 46: 32-47, 2002) as well as from chickens and ducks. These isolates have been associated with enteric and respiratory disease (Fahey, J. E., and Crawley, J. F., Can. J. Comp. Med. 18: 13-21, 1954), viral arthritis/tenosynovitis (Glass, S. E., et al., Avian Dis. 17: 415-424, 1973), malabsorption and stunting syndrome (Rosenberger, J. K., In: Diseases of poultry, 11th ed. Barnes, H. J., et al., eds. Iowa State University Press, Ames Iowa, pp. 284-293, 2003). Not all reoviruses are highly virulent, as they can be isolated from chickens or turkeys exhibiting no clinical signs of disease.
RSS is a disease of domesticated chickens that causes a variety of symptoms, such as delayed growth, lack of flock uniformity, a small liver with an enlarged gall bladder, pale, thin, almost translucent, intestinal walls, large amounts of fluid inside the small and large intestines, occasional increased amount of pericardial fluid, and sporadic white, or cream-colored, plaques in individual proventricular glands. Various microscopic lesions have also been observed, and frequently noted as multiple cysts in the intestinal crypts. The early lesion is clinically considered to be a form of cystic enteropathy, and which evolves into an inflammatory lesion causing cystic enteritis. As the lesions progress, they may result in shortening and clubbing of the intestinal villi. Outbreaks of RSS reduce the growth rate, body weight, and size, and increase the mortality in affected chicken populations.
Runting-Stunting Syndrome can been reproduced in the clinic. Gavage inoculations with intestinal contents from affected chickens, for example, cause RSS in the inoculated chickens. Inoculation with filtered gut contents from affected chickens can also cause RSS, suggesting that a virus is responsibly for the syndrome, since the filters used to inoculate the gut contents are able to exclude bacteria. RSS has also been reproduced in experiments that place healthy broiler chickens on litter contaminated by affected chickens.
Runting-Stunting Syndrome has a significant economic impact on the chicken farming industry. Delayed growth during the first few weeks of age, for example, increases the cost of feed conversion. In 2004, broiler companies across the southeast United States began seeing more cases of Runting-Stunting Syndrome (RSS) during the winter and spring seasons. Losses due to RSS at one company were estimated to be over $100,000 per week per million birds. These impacts demonstrate a continuing need for compositions and methods for ameliorating at one or more symptoms of RSS, for identifying and characterizing the causative agent(s) of RSS, and for preventing the onset of RSS in chickens.
While viral agents, environmental conditions, and genetic factors are all believed to play a role in determining the susceptibility of chickens to RSS, vaccines against various infectious agents hold much promise in containing this and related diseases. Vaccines can be divided into two general groups: live (attenuated) vaccines, and inactivated vaccines. Live vaccines can present of all the relevant immunogenic determinants of an infectious agent in their natural forms to the host's immune system, and because they can multiply in the vaccinated host, only require a small amount of the immunizing agent. Safety is often a concern with live vaccines, however, as they may induce disease in immuno-compromised animals, or they may revert to a virulent form, leading to more serious infections. Live vaccines may also impair reproductive function. Inactivated vaccines by comparison are generally far safer than live vaccines. One major disadvantage, however, is their intrinsically low immunogenicity (i.e., ability to trigger the host's immune system). Adjuvants with significant immunostimulatory capabilities are often necessary, then, to augment the immunogenicity of inactivated immunogens to reach a minimum potential suitable for preventing disease in a vaccinated bird or preventing the spread of infection and disease to unvaccinated birds.
Vaccination of poultry is useful for several reasons. One purpose is to prevent egg production losses in commercial layers. Vaccines may also be used to reduce the level of transmission by eggs in breeding stock or as a tool for eradicating disease in infected flocks on multi-age production sites. Thus there remains a need for safe, efficacious, and inexpensive vaccines that sufficient to protect poultry susceptible to etiological agents, such as avian reoviruses, that may cause Runting Shunting Syndrome or related diseases. Vaccines effective against avian reoviruses, for example, may optionally be combined with vaccines that protect poultry from other commercially-troublesome infectious diseases. The formulation should also be stable, and provide lasting protection without undesirable side effects.